In the EU Joint Clinical Assessment, Member States define the PICOs, and the part you cannot easily guess is the comparator. Population follows the label, outcomes share a common core, but every country selects comparators with its own rule, filtered by what is reimbursed and shifting over time. Predicting your PICOs is, in practice, predicting comparators country by country, early enough to build the evidence before the 100-day clock starts.
Population is predictable. The comparator is not.
A PICO has four parts (Population, Intervention, Comparator, Outcome), but they are not equally hard to anticipate. Your intervention is your product in the indication you are seeking. The population largely follows the marketing-authorisation label. Outcomes share a common core across Europe (efficacy, quality of life, safety), with national differences in emphasis and hierarchy. The comparator is where the uncertainty lives, and it is roughly 80% of the work of predicting a PICO.
Predicting your PICOs is, in 80% of the effort, predicting comparators, country by country.
Why the comparator is hard: every country picks it differently
Two layers multiply. First, the standard of care in each country, taken from national clinical guidelines (or European ones, such as ESMO, where no national guideline exists). Second, and this is the biggest source of divergence, each agency applies its own comparator-selection rule. Some want the most cost-effective option, some the treatment most likely to be replaced, some every locally-relevant comparator. Two modulators sit on top: reimbursement (several countries only accept a comparator that is reimbursed in their system) and time (standards, guidelines and approvals move, so a prediction expires).
| Member State | How it selects the comparator |
|---|---|
| Germany ★ | All locally-relevant comparators |
| France | National clinical practice |
| Italy ★ | All relevant comparators |
| Spain ★ | All locally-relevant comparators |
| Portugal ★ | All relevant comparators (up to 7) |
| Ireland ★ | All relevant comparators |
| Netherlands | Most cost-effective comparator |
| Sweden | Most cost-effective comparator |
| Denmark | All commonly used treatments |
| Norway | Treatment most likely to be replaced |
| Belgium | Treatment that will be replaced |
| Romania | Reimbursed comparators only |
| Greece | A single comparator |
★ These five (Germany, Italy, Spain, Portugal and Ireland) demand every locally-relevant comparator. Portugal alone can ask for up to seven. They are what decides the size of your evidence package, so identifying them early matters more than almost anything else in the scope.
Up to 80% of PICOs need an indirect comparison
You will rarely have a head-to-head trial against every comparator every country asks for. So most PICOs, up to 80%, require an indirect treatment comparison (an ITC or network meta-analysis), or a documented strategic justification when one is not feasible. Each missing comparator is a synthesis you have to build. And because you cannot reuse the JCA evidence in your later national submissions, the prediction shapes your country-by-country evidence strategy too.
Two things quietly move the target
- Label uncertainty. The scope is fixed before the CHMP adopts the final indication. If the final label does not match the evidence you built, the assessment can have to restart for that product, so it pays to anticipate the plausible label variants, not just one.
- Time. Comparator landscapes drift as new treatments are approved and reimbursed. Widen the window and the number of consolidated PICOs goes up. A prediction is a snapshot; it has to be kept alive.
Why this has to happen early
From the consolidated scope you have roughly 90 to 100 days (60 if accelerated) to deliver a multi-PICO dossier, with a hard cap 45 days before the CHMP opinion. Three months from a standing start is not enough. The teams that cope have already built their evidence syntheses for the PICOs they expected, which is only possible if they anticipated, reliably, what they would be asked. Done well, receiving the scope stops being a 100-day panic and becomes an assembly job: confirm the delta, slot in what is ready.
Walk into the scope with the evidence already built
JCA Studio is being built to help market-access and HEOR teams anticipate their PICOs and comparators across Member States, so the 100-day clock becomes an assembly exercise rather than a scramble. Human-in-the-loop by design: your HEOR and biostatistics sign off every analysis.
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